Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes

Adipose tissue maintains metabolic homeostasis during fasting and fed conditions. When nutrients are plentiful, anabolic signaling is mediated by insulin, stimulating adipocytes to take up glucose for energy storage. In the absence of nutrients, catabolic signaling initiates lipolysis, or the release of lipids for energy use, and is mediated by catecholamines. These opposing pathways are evolutionarily conserved and prevent futile cycling, but can lead to metabolic disorders such as insulin resistance if not properly regulated. Here we define a novel mechanism whereby lipolysis inhibits insulin-stimulated glucose uptake in adipocytes. This signaling mechanism likely contributes to insulin resistance when lipolysis is active, such as during high stress or obesity, and this new understanding may lead to novel treatment approaches for hyperglycemia.